Background: Occupational exposure as a firefighter causes cancer, as determined by IARC, including sufficient evidence for bladder cancer and mesothelioma and strong evidence for five carcinogenic mechanisms, including genotoxicity, epigenetic alterations, oxidative stress, chronic inflammation, and modulation of receptor-mediated effects. Furthermore, firefighters are exposed to carcinogenic products of combustion and in the United States (U.S.) have higher concentrations of some per- and polyfluoroalkyl substances (PFAS) than other essential workers and the general population. Molecular ‘omic’ analyses (including epigenomics, proteomics, and metabolomics) can provide a wealth of biomarkers of effect in firefighters, which can in turn be used to evaluate the potential beneficial effects of preventive interventions. Supported by the IARC determination, firefighters globally are willing to take evidence-based steps to reduce their exposures and mitigate the associated toxic effects.
Objectives: The purpose of this presentation is to summarize knowledge gained from omic analyses in firefighters, including information on the contribution of various exposures on omics biomarkers, and preliminary data on the effectiveness of interventions to mitigate these adverse effects.
Methods: Blood and urine samples were collected from U.S. recruit and incumbent firefighters in the Fire Fighter Cancer Cohort Study (FFCCS) at enrollment, approximately every two years, and after specified exposures. DNA methylation (DNAm), microRNA (miRNA) expression, and proteins were measured in blood and untargeted metabolites measured in urine. Information on years of firefighter service was collected via survey, and serum was analyzed for PFAS concentrations. Interventions tested included time-restricted eating (intermittent fasting), exercise, blood or plasma donation, and nutraceutical supplementation.
Results: Years of firefighting, cumulative fire response hours or runs, and/or serum PFAS concentrations are associated with DNAm alteration within genes associated with cancers and biological age acceleration approximated by epigenetic clocks. Years of firefighting, wildland-urban interface (WUI) fire exposure, and serum PFAS concentrations are associated with miRNA expression linked to cancers and other disease outcomes. Structural, wildland, WUI, and training fire exposure are associated with changes in urine metabolomics linked to oxidative stress and other cancer-related pathways. Exposures to the January 2025 Los Angeles area urban conflagrations are associated with changes in serum proteins linked to oxidative stress and other toxic mechanisms. Time-restricted eating is associated with a reduction in epigenetic age, and plasma donation is associated with reduced serum PFAS. The effects of blood or plasma donation or nutraceutical supplementation on DNAm will be available before the IARC meeting.
Conclusions/Implications for practice or policy: Omics analyses have revealed a wealth of information on the cellular effects of firefighter exposures associated with both cancer and other disease risk, as well as the effectiveness of cancer prevention interventions.